The major objective of the program project is to study the natural history of perinatal cytomegalovirus (CMV) infections in mothers, infants and children by large scale, prospective and longitudinal investigations. The CMV studies include in the mothers: 1) the role of recurrent versus primary infection in intrauterine and intrapartal transmission, 2) mechanisms of fetal transmission with recurrent maternal infection and, 3) effect of pregnancy hormones on growth of CMV. In infants and children they include studies on: 1) long-term developmental outcome, 2) assessment of immunologic assays for detection of silent infection in the newborn, 3) pathogenetic studies of severe disease and, 4) nature of immune complex formation in congenital CMV. In addition, longitudinal studies of the humoral and cellular immune response in the maternal, congenital and natal infections are to be determined and related to virologic and clinical parameters over time. Human strains of virus are to be also genetically analyzed and related to the disease state in man to search for microbial virulence factors.